Central nervous system control of the airways: pharmacological implications

Autonomic innervation of the airways is derived primarily from the parasympathetic nervous system. Preganglionic fibers originating in the brainstem project to parasympathetic ganglion neurons, which regulate airway smooth-muscle tone, glandular secretion and blood-vessel diameter. Airway preganglionic nerve activity is regulated by subsets of pulmonary and extrapulmonary afferent nerve fibers, which continuously provide polysynaptic input to brainstem preganglionic nuclei. Each of these synapses in the central nervous system is a potential site for therapeutic intervention. Potential targets include increasing opioid, GABAergic and serotonergic controls on central neurons, and blockade of tachykinin and glutamate receptors. Unfortunately, much is still unknown about the control of airway nerves at the level of the central nervous system. Recently, however, interaction between vagal afferent nerve subtypes regulating airway function has been described. This interaction, made possible by their convergence at key sites of integration in the brainstem, may lead to central sensitization analogous to that described in somatic pathways regulating pain sensation. Improved understanding of the central pharmacology of airway reflexes may provide novel therapeutics for treating symptoms associated with respiratory disorders such as chronic obstructive pulmonary disease, asthma and sleep-disordered breathing.